Aptamers have emerged as one of the most promising classes of drug leads and diagnostic ligands presently available. Aptamers, nucleic acid ligands derived from large combinatorial libraries, typically have affinities and specificities that rival antibodies, yet they have a number of significant advantages for therapeutic and diagnostic applications. Unfortunately, the existing process for aptamer development is low-throughput and tedious as DNA or RNA libraries are screened against only a single target. This project focuses on developing the methods and tools to allow large combinatorial to be screened against arrays of thousands of proteins simultaneously. Such protein arrays are increasing available with content of high therapeutic and diagnostic value. The key to achieving this is developing the necessary steps to decipher which aptamers (once selected) correspond to which target. So-called next generation sequencing will greatly enable the proposed process coupled with the necessary sequence-tagging approaches developed in this project. Once our massively parallel aptamer selection process is developed, we will be in a position to create high affinity aptamer ligands to thousands of proteins in roughly 1 week. The developed ligands can then be further characterized as promising drug candidates, diagnostic labels, and other research applications perhaps eventually including personalized medicine.